Patients with gastroparesis often suffer with chronic gastrointestinal symptoms that are not adequately treated due, in part, to a lack of understanding of the underlying pathophysiology and due, in part, to a lack of effective treatments. The participation of Temple University Gastrointestinal Motility Center in the NIH/NIDDK Gastroparesis Clinical Research Consortium and the proposed studies will help achieve the broad, long term objectives of improving the diagnosis and treatment of patients with gastroparesis. Temple s exceptionally well qualified to be one of the clinical centers in this consortium. Temple has clinical expertise and an active research program in the evaluation and treatment of patients with gastroparesis. Our short-term study proposal is designed to test the hypotheses that botulinum toxin injection into the pylorus improves dyspeptic symptoms and accelerates gastric emptying in a subgroup of patients who can be identified with physiologic testing. We propose a prospective, multi-center, randomized, placebo- controlled, double blind study to assess the efficacy of botulinum toxin on symptoms and gastric emptying. We will analyze factors that may be predictive of a beneficial response including type and severity of gastroparesis, baseline pyloric pressure, gender, and specific symptom profiles. Our long-term study proposal is a longitudinal cohort study of patients with gastroparesis designed to understand the causes and improve the treatment of symptom exacerbations in patients with gastroparesis. In this study, patients' symptomswill be followed on a regular basis using an Internet-based telemedicine system. This will allow several antecedent factors to be followed that may be responsible for symptom exacerbation including glucose control, dietary intake, psychological stress, and inflammation. Additionally, the symptomaticresponse of patients to two agents (domperidone and desipramine) that may be effective in improving symptoms but target different pathophysiologic processes will be assessed. Domperidone is a prokinetic/antiemetic agent, whereas desipramine is a symptom modulator/antidepressant agent. The proposed protocols will help define patient populations that may respond to different types of treatments for gastroparesis. The protocols use novel diagnostic tests to better define the pathophysiology of gastroparesis. These studies will also better define the disease course of patients with gastroparesis.